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Daily Interferon Alfacon-1 Treatment with Ribavirin Appears Promising for HCV Infection

February 7, 2001 (Philadelphia)
—An accelerated, daily regimen of interferon alfacon-1 (Infergen, Amgen) plus treatment with a standard, widely used antiviral agent is a promising treatment option for patients infected with the hepatitis C virus (HCV), according to a recent randomized study.

The study suggests there may be a future for the novel combination therapy in patients with HCV infection. The new approach uses daily, or induction, interferon dosing instead of the standard three-times-weekly regimen. It also relies on the antiviral drug ribavirin to help keep the
virus away once it has been largely eliminated. Daily dosing is thought to increase the effectiveness of interferons, which modulate the body’s immune responses.

Earlier research on interferon alfacon-1 had suggested that daily 9 mcg or 15 mcg doses may be more effective against HCV infection, but also as safe and well tolerated as the conventional regimen of 9 mcg three times per week. A separate group of studies indicated that the addition of ribavirin to a different form of interferon (interferon alfa2b) might eliminate HCV from the bloodstream more effectively than interferon alone.

The new study was designed to show whether a fusion of those two promising approaches daily dosing and combination therapy might produce better results than are possible with daily interferon alfacon-1 alone, according to the study’s lead investigator, Paul J. Pockros, MD.

The earlier studies suggested that adding ribavirin to interferon seems to prevent relapse, said Dr. Pockros, who is head of the Division of Gastroenterology and Hepatology at the Scripps Clinic and Research Foundation in La Jolla, California. So, if we improved the initial response rates using induction interferon dosing, by adding ribavirin we would hope to hold that improvement to the end of treatment.

The study included 40 patients with HCV infection and liver enzyme test results that signaled active hepatitis, Dr. Pockros said. The patients had never before been treated with an interferon or with ribavirin. Twenty-one patients were randomly assigned to receive daily treatment with 9 mcg interferon alfacon-1 for 48 weeks. The remaining 19 patients received the drug on the same dosing schedule along with ribavirin at 1,000-1,200 mg daily, also for 48 weeks. Dr. Pockros reported the study’s 24-week findings at the October 2000 scientific meeting of the American Association for the Study of Liver Diseases in Dallas.

Fifty-eight percent of patients in the combined-therapy group achieved a biochemical remission (i.e., normal blood levels of alanine aminotransferase) compared to only 38% of those who received interferon alone. Elevated levels of the enzyme would have indicated worsened liver disease.

Although most patients in the two groups are tolerating the treatment well, Dr. Pockros said, one more patient in the combination-therapy group than in the interferon-only group six and five patients, respectively went off assigned treatment because of poor tolerance. The regimen is proving somewhat difficult for the patients, whether the interferon is in combination with ribavirin or by itself, he said. The tolerability of daily interferon is a little less than a regimen of three-times-a-week, which makes sense.

The two treatments were about equal in their ability to eliminate the viral infection. Statistically similar proportions of patients (52% receiving interferon and ribavirin; and 42% on monotherapy) had no detectable levels of the virus in their blood, as determined by concentrations of the viral RNA.

These similar viral response rates were not a surprise, Dr. Pockros said, because both groups received the same amount of interferon alfacon-1. But the purpose of the other agent, ribavirin, is to suppress resurgence of the virus after its levels have been reduced. Thus, one would expect that by the end of therapy at 48 weeks, the patients getting the combination of Infergen and ribavirin would show a higher sustained response rate, he said.

Patients in the study’s two treatment groups, Dr. Pockros said, were typical of those with HCV infection that we see in the United States. Before therapy, they were similar with respect to average age, the ratio of men to women, and average blood HCV concentrations. After treatment started, the patients underwent regular clinical evaluation and laboratory measurement of red and white blood cells, platelets, hemoglobin, and other blood factors to assess the safety and tolerability of each treatment regimen.

Although results of those assessments were generally the same in both groups, reduced levels of hemoglobin over the first 24 weeks of therapy were more often observed among patients on the Infergen-ribavirin combination. The reduced levels were a sign of hemolytic anemia, a recognized, non-life-threatening side effect of ribavirin.

Combined therapy was also associated with transient, asymptomatic decreases in serum calcium levels. The reduced serum calcium levels were observed in about 58% of patients who took both drugs and in only 19% of those who took only the interferon. We aren’t sure why we saw it, but it didn’t have any lasting effects, and it didn’t recur after the first 12 weeks of therapy, Dr. Pockros said.

Whether the combination regimen produces a sustained response will have to await completion of the 48-week data analysis. Dr. Pockros and his colleagues plan to have those results sometime early this year. But at this point, he said, daily combination therapy appears about as safe as
interferon alfacon-1 alone and may prove to be a promising treatment option for patients with HCV infection.

The study was conducted at four major U.S. medical centers: Scripps Clinic and Research Foundation, La Jolla, CA; the Charlotte Clinic, Charlotte, NC, the University of Miami, FL; and the University of California, San Francisco.